Download Biochemistry Metabolic pathways - LIMES

Biochemistry
Metabolic pathways
21.11.2016 – 16.12.2016
Gluconeogenesis
Gerhild van Echten-Deckert
Tel. 73 2703
E-mail: [email protected]
www.limes-institut-bonn.de
Gluconeogenesis
Glycolysis
7 glycolytic enzymes catalyze
the transformation of non-carbohydrate
metabolites including lactate, pyruvate,
amino acids into glucose.
3 energy consuming bypass
reactions are the prize
for an independent regulation
of the two opposing pathways
Lehninger Principles of Biochemistry
Nelson & Cox
Conversion of pyruvate into PEP is mediated by oxaloacetate
Biotin is the prosthetic group of pyruvate carboxylase
(Vitamin B7/Vitamin H)
Biochemistry. Voet & Voet
Two-phase reaction mechanism of pyruvate carboxylase
Biochemistry. Voet & Voet
The reaction mechanism of PEPCK
Biochemistry. Voet & Voet
The allosteric modulation of key enzymes of Gluconeogenesis and Glycolysis
Gluconeogenesis
Glycolysis
Citrate
Glucokinase = Hexokinase IV
AMP
Biochemie u. Pathobiochemie.
Löffler & Petrides
Coordinated transcriptional regulation of Gluconeogenesis and Glycolysis
by insulin and cAMP in liver
(Glucagon)
(Glucagon)
Gluconeogenesis
Glycolysis
Biochemie u. Pathobiochemie.
Löffler & Petrides
Insulin activates PKB via PI-3 kinase
A Ras independent pathway activates Protein Kinase B
Lodish et al. Molecular Biology of the Cell
Cell transformation is accompanied
by a switch to ATP generation
via glycolysis. Thus assuring cellular
energy homeostasis under hypoxic
conditions. Consequently glucose
transporters and glycolytic enzymes
are overproduced in tumours.
p53: tumour suppressor protein;
protects cells against unrestrained
growth; is most frequently mutated
gene (> 50%) in human cancer.
The high rate of glycolysis in tumour cells is used in diagnosis
Phosphorylation of 18F-labelled 2FdG by hexokinase traps the FdG in cells as
6-phosphoFdG, which can be detected by positron emission from 18F.
Detection of cancerous tissue by positron emission tomography (PET)
CT
PET
False color